Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation.

Recent studies have shown that G-protein-coupled receptors (GPCRs) can assemble as high molecular weight homo- and hetero-oligomeric complexes. This can result in altered receptor-ligand binding, signaling, or intracellular trafficking. We have co-transfected HEK-293 cells with differentially epitope-tagged GPCRs from different subfamilies and determined whether oligomeric complexes were formed by co-immunoprecipitation ...
and immunoblot analysis. This gave the surprising result that the 5HT(1A) receptor was capable of forming hetero-oligomers with all GPCRs tested including the 5HT(1B), 5HT(1D), EDG(1), EDG(3), GPR(26), and GABA(B2) receptors. The testing of other GPCR combinations showed similar results with hetero-oligomer formation occurring for the 5HT(1D) with the 5HT(1B) and EDG(1) receptor. Control studies showed that these complexes were present in co-transfected cells before the time of lysis and that the hetero-oligomers were comprised of GPCRs at discrete stoichiometries. These findings suggest that GPCRs have a natural tendency to form oligomers when co-transfected into cells. Future studies should therefore investigate the presence and physiological role of GPCR hetero-oligomers in cells in which they are endogenously expressed.
Mesh Terms:
Cell Line, GTP-Binding Proteins, Humans, Immunoblotting, Kidney, Mutagenesis, Site-Directed, Protein Subunits, Proto-Oncogene Proteins c-myc, Receptor, Serotonin, 5-HT1B, Receptor, Serotonin, 5-HT1D, Receptors, Cell Surface, Receptors, Serotonin, Receptors, Serotonin, 5-HT1, Recombinant Proteins, Restriction Mapping, Transfection
J. Biol. Chem.
Date: May. 03, 2002
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